Temporal dissection of Rai1 function reveals brain-derived neurotrophic factor as a potential therapeutic target for Smith–Magenis syndrome
Supported by SMSRF, Dr. Wei-Hsiang Huang’s team at McGill University studied the function of Rai1, the disease-causing gene of SMS, at different developmental stage. The team discovered that Rai1 is essential in regulating energy homeostasis throughout life. More importantly, they found that Rai1 is required in the adult brain to maintain the level of brain-derived neurotrophic factor (Bdnf), an important neurotrophic protein. The team took a genetic approach to express human Bdnf in SMS mice and found that globally expressing human Bdnf in early development prevents the development of SMS-like obesity, metabolic-like syndrome, and social interaction deficits. This is remarkable because for the first time, social interaction and obesity can be successfully treated by delivering a single molecule into SMS mice. In the future, the team will focus on using a more clinically translatable pharmacological approach to increase Bdnf signaling in the mouse brain to treat SMS.
